Genotoxicity and physicochemical characteristics of traffic-related ambient particulate matter

Exposure to ambient particulate matter (PM) has been linked to several adverse health effects. Since vehicular traffic is a PM source of growing importance, we sampled total suspended particulate (TSP), PM(10), and PM(2.5) at six urban locations with pronounced differences in traffic intensity. The mutagenicity, DNA-adduct formation, and induction of oxidative DNA damage by the samples were studied as genotoxicological parameters, in relation to polycyclic aromatic hydrocarbon (PAH) levels, elemental composition, and radical-generating capacity (RGC) as chemical characteristics. We found pronounced differences in the genotoxicity and chemical characteristics of PM from the various locations, although we could not establish a correlation between traffic intensity and any of these characteristics for any of the PM size fractions. Therefore, the differences between locations may be due to local sources of PM, other than traffic. The concentration of total (carcinogenic) PAHs correlated positively with RGC, direct and S9-mediated mutagenicity, as well as the induction of DNA adducts and oxidative DNA damage. The interaction between total PAHs and transition metals correlated positively with DNA-adduct formation, particularly from the PM(2.5) fraction. RGC was not associated with one specific PM size fraction, but mutagenicity and DNA reactivity after metabolic activation were relatively high in PM(10) and PM(2.5), when compared with TSP. We conclude that the toxicological characteristics of urban PM samples show pronounced differences, even when PM concentrations at the sample sites are comparable. This implies that emission reduction strategies that take chemical and toxicological characteristics of PM into account may be useful for reducing the health risks associated with PM exposure.     

Increasing trend of Cesarean deliveries in HIV-infected women in the United States from 1994 to 2000

BACKGROUND: Meta-analysis and randomized clinical trial results reported in June 1998 indicated a significant reduction in perinatal HIV transmission rates among mothers undergoing a cesarean section (C-section). OBJECTIVE: The objective of this study was to examine recent trends in and factors associated with C-section deliveries among HIV-infected women in the United States. DESIGN: A multisite pediatric medical record review of a cohort of HIV-exposed and HIV-infected infants in the Pediatric Spectrum of HIV Disease (PSD) Cohort study (n = 6467) and the national Pediatric HIV/AIDS Reporting System (HARS) (n = 8,306) was conducted. SETTING/PATIENTS: All infants born between 1994 and 2000 to HIV-positive mothers referred to the PSD study or to a Pediatric HARS hospital or clinic site were enrolled. RESULTS: The proportion of deliveries by C-section was steady at about 20% from 1994 through June 1998. From July 1998 through December 2000, this proportion increased to 44% in the PSD study and to nearly 50% in the Pediatric HARS. On analysis by multiple logistic regression, delivery of infants by C-section was associated with the release of study results (OR = 2.83), delivery in four PSD sites in reference to Texas (OR: 2.02-1.43), having private medical care reimbursement (OR = 1.62), and having maternal prenatal care (OR = 1.43). CONCLUSIONS: The PSD and Pediatric HARS data demonstrate a sharp increase in C-section rates mainly among HIV-infected women in the United States after the release of the meta-analysis and randomized clinical trial results in 1998. This finding highlights the rapid impact of study results on obstetric practice. It underscores the critical role of prenatal care in offering perinatal interventions such as scheduled C-section when indicated to reduce the likelihood of HIV transmission.     

Preliminary reliability and validity of the Clinician-Administered PTSD Scale for schizophrenia

This study provides preliminary psychometric support for a version of the Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale (CAPS; D. D. Blake et al., 1990) adapted for use with patients with schizophrenia (CAPS-S; J. S. Gearon. S. Thomas-Lohrman, & A. S. Bellack, 2001). Nineteen women with schizophrenia and co-occurring illicit drug use disorders were administered the CAPS-S, the Structured Clinical Interview for DSM-IV diagnoses (SCID). and scales measuring trauma-related psychopathology. The results indicate that the CAPS-S can distinguish between those with and without PTSD and that the symptom clusters measure unified constructs. Interrater and test-retest reliability were high for PTSD diagnosis and symptom clusters. Solid convergent validity was demonstrated between the CAPS-S and SCID-based PTSD diagnoses and the Impact of Event Scale. There is also preliminary evidence of discriminant validity. These results support the use of the CAPS-S in women with schizophrenia.     

Factor Structure, Reliability, and Validity of the Pain Catastrophizing Scale

The Pain Catastrophizing Scale (PCS; Sullivan et al., Psychol. Assess. 7, 524–532, 1995) has recently been developed to assess three components of catastrophizing: rumination, magnification, and helplessness. We conducted three studies to evaluate the factor structure, reliability, and validity of the PCS. In Study I, we conducted principal-components analysis with oblique rotation to replicate the three factors of the PCS. Gender differences on the original PCS subscales were also analyzed. In Study II, we conducted confirmatory factor analyses to evaluate the adequacy of fit of four alternative models. We also evaluated evidence for concurrent and discriminant validity. In Study III, we evaluated the ability of the PCS and subscales to differentiate between the responses of clinic (students seeking treatment) and nonclinic undergraduate samples. Also, in the clinic sample, we evaluated evidence of concurrent and predictive validity for the PCS. The internal consistency reliability indices for the total PCS and subscales were examined in all three studies. Limitations and future directions are discussed.     

Selective inhibition by dactinomycin of NANC sensory bronchoconstriction and [125I]NKA binding due to NK-2 receptor antagonism.

In the present study, dactinomycin (10(-5) M) inhibited the non-adrenergic, non-cholinergic bronchoconstriction upon antidromic vagal nerve stimulation (1 Hz for 1 min) in the isolated perfused guinea-pig lung by 84%. The release of calcitonin gene-related peptide was unchanged, however, suggesting a postjunctional action. Dactinomycin (10(-5), 5 x 10(-5) M) also reduced non-adrenergic non-cholinergic bronchial contractions (maximally by 75%) induced by electrical field stimulation or capsaicin, while the cholinergic component and non-adrenergic non-cholinergic relaxation remained intact. The neurokinin-2 receptor antagonist L-659,877 (10(-6) M) had a similar effect as dactinomycin, inhibiting the non-adrenergic non-cholinergic bronchial contractions by 69%, while the neurokinin-1 receptor antagonist CP-96,345 (10(-6) M) had no effect. The bronchoconstriction evoked by neurokinin A, the selective neurokinin-2 receptor agonist Nle10neurokinin A (4-10) and capsaicin was markedly inhibited by dactinomycin while the contraction induced by substance P (SP), the selective neurokinin-1 receptor agonist Sar9Met(O2)11SP, endothelin-1 and acetylcholine was not affected. In autoradiographic experiments on guinea-pig lung, [125I]neurokinin A-labelled sections showed dense binding in the bronchial smooth muscle layer. Dactinomycin inhibited the specific binding of [125I]neurokinin A in a concentration-dependent manner (IC50 = 6.3 x 10(-6) M) and 66% of [125I]neurokinin A total binding was inhibited by 10(-4) M dactinomycin. In the rat colon, [125I]neurokinin A binding to neurokinin-2 sites on circular smooth muscle was inhibited by dactinomycin with an IC50 value of 7.9 x 10(-6) M. Dactinomycin failed to reduce increased nerve-evoked contractions or those caused by Nle10neurokinin A (4-10) per se in the rat vas deferens, which are considered to be mediated by neurokinin-2 receptor activation. In the rat portal vein, dactinomycin did not influence the contractions caused by the neurokinin-3 selective agonist Pro7neurokinin B. In conclusion, dactinomycin selectively inhibited neurokinin-2 receptor activation in guinea-pig lung and rat colon, but not in rat vas deferens, which may depend on the existence of different neurokinin-2 receptor subtypes. Neurokinin A is most likely the main endogenous excitatory non-adrenergic non-cholinergic transmitter in guinea-pig bronchi.     

Detecting DNA repair capacity of peripheral lymphocytes from cancer patients with UVC challenge test and bleomycin challenge test

The objective of this study was to evaluate DNA repair capacity of cancer patients with the bleomycin (BLM) challenge test and the UVC challenge test. The human peripheral lymphocytes were collected from 33 patients with different kinds of cancers and 33 controls in the same hospital. The lymphocytes of each subject were divided into two groups: (1) In the BLM challenge test, the lymphocytes were treated with BLM (20 microgml(-1)) for 30 min, and repaired for 15 min. The DNA damage before and after BLM exposure was detected with comet assay to assess DNA repair capacity. (2) In the UVC challenge test, the lymphocytes were exposed to UVC (254 nm) at the dose of 1.5 Jm(-2). DNA damage of lymphocytes was measured before UVC exposure and at 90 and 240 min after UVC exposure using comet assay, then DNA repair percentage (DRP) was calculated. The results of this study indicate that the average DRPs of cancer patients were 75.63 +/- 3.11 and 68.98 +/- 4.19% calculated with tail length (TL) and tail moment (TM), respectively, in the BLM challenge test, which were significantly lower than those (91.11 +/- 1.09 and 88.19 +/- 1.71%) of controls (P < 0.01). Also, the mean DRPs of cancer patients were 49.19 +/- 3.47 and 58.27 +/- 3.64% calculated with TL and TM, respectively, in the UVC test, which were significantly lower than those (77.52 +/- 2.06 and 83.12 +/- 2.36%) of controls (P < 0.01). The correlation between the DRPs (%) drawn with TL and TM in the BLM test or between the DRPs (%) drawn with mean TL and mean TM in the UVC challenge test were significant (P < 0.05). The DNA repair capacity measured with the BLM and UVC challenge tests in 33 cancer patients was significantly lower than that in controls.     

Thymic stroma is required for the development of human T cell lineages in vitro

Development of the T cell lineage is characterized by the homingof hematopoietic precursors to thymus, followed by their acquisitionof receptors for antigen. T cell receptors are ß or heterodimers associated with CD3 (TCR-CD3). Very early T cellprecursors in humans have been characterized as CD7+45+ cellswhich lack the T cell differentiation antigens CD1, CD2, CD3,CD4, and CD8. A phenotypically equivalent early thymocyte populationalso occurs in postnatal life, and we have previously shownthat interleukin 2 (IL2) promotes the development in vitro ofboth the ß and the T cells from these early thymocytes.Here we have analyzed the requirements of the induction of theIL2 pathway in early thymocytes, and their developmental potential.We show that: (I) thymic stromal cells, which are present inthymocyte suspensions, are necessary to induce the IL2 pathwayand the development of ß or T cell lineages fromearly thymocytes in vitro; and (II) when removed from the invivo environment, early thymocytes can develop in vitro intoTCR-CD3^– cells of the natural killer (NK) lineage. Weconclude that CD7+45+, CD1–2–3–4–8–early thymocytes are multipotential progenitors that, at least,have the capacity to develop into ß or T cell andNK lineages. The analysis of the mechanisms of generation andselection of human T and NK cell diversity, not feasible inbone marrow cultures, is now possible.     

Changing and sustaining medical students' knowledge, skills, and attitudes about patient safety and medical fallibility.

PURPOSE: To study the effects of a patient safety and medical fallibility curriculum on second-year medical students at the University of Missouri-Columbia School of Medicine in 2003-2004. METHOD: Students completed a knowledge, skills, and attitudes questionnaire before the curriculum, after the final learning experience, and one year later. A 95% confidence interval (CI) for paired differences assessed change over time. At one year, students also responded to items about their use of the curriculum, error reporting, and disclosure experiences. RESULTS: Fifty three of 92 students (55%) completed the questionnaire at all three assessment points. Students' eight items and the calculated knowledge score improved after the curriculum but only seven of these improvements were sustained one year. Responses to seven items did not change and five changed in an undesired direction after the curriculum and/or after one year. Seventy two students completed the self-reported behavior questions at one year. More than half reported using what they learned in the curriculum. Although 76% of students reported observing an error, 71% of these disclosed an error to their peers, 56% to a resident, and 46% to faculty. Only 7% reported an error using our electronic error reporting system. CONCLUSIONS: The curriculum led to changes in second-year medical students' knowledge, skills, and attitudes, but not all of the changes were sustained at one year, were in the desired direction, or were supported by their self-reported behaviors. The extent to which other informal or hidden curriculum experiences reversed the gains and affected the changes at one year is unknown.     

Roberts铜盐法测定蔗汁葡聚糖含量的热效应——淀粉对受热蔗汁葡聚糖测定的影响

作者从研究中发现:用Roberts铜盐法测定蔗汁样本葡聚糖含量时,所得结果与蔗汁的受热有关,受热蔗汁的测定值高于真实值,作者将这种现象暂称为Roberts铜盐法测定蔗汁样本葡聚糖含量的热效应。研究表明:蔗汁中的淀粉是引起热效应的重要因素。本文最后提出了一种由淀粉引起的热效应的可行校正方法。